Harboring a particular hatred for the Brotherhood of Steel, he joins a raider group called Cyphers which are the exact opposite of the Brotherhood in their view of technology: instead of worshipping it, they hate it. However, even amongst them he is considered too reactionary for his wish to wage war on the BoS.

During research he learns about the G.E.C.K. and steals the prototype from the Nursery. As Miles heads down to the Gulf of Mexico, the device starts working, leaving a trail of strange plant life all over the countryside. Arriving at the Gulf, he spends the next 5 years improving the G.E.C.K. However, the increased potence of the device has strange effects on the FEV-infected environment, transforming the landscape and eventually even submerging his own base in the Gulf. Protecting in with an organic shell with airholes reaching to the surface, Reese continues his work towards the goal of a new world without humans.

Out of his hatred for the Brotherhood, he decides to separate them from their technology to see how they would fare without it. To this end he uses the Jackals, ordering them to steal it. Unknown to them, Miles has infected them with a bio-organism created by the G.E.C.K. which acts as a mini-bio-bomb of sorts, allowing Reese to detonate his minions and the stolen Brotherhood technology with them when he is ready to activate his New Eden device, starting world over.